National Institute of Mental Health (NIMH) scientists have linked a gene variant that reduces dopamine activity in the prefrontal cortex to poorer performance and inefficient functioning of that brain region during working memory tasks, and to slightly increased risk for schizophrenia.

The finding, which must still be confirmed by independent teams of investigators, emerged from an ongoing study of people with schizophrenia and their siblings. The study is among the first to suggest a mechanism by which a gene might confer susceptibility to a mental illness, say the researchers. Daniel Weinberger, M.D., Michael Egan, M.D., NIMH Clinical Brain Disorders Branch, and colleagues, report on their results in the May 29, 2001 Proceedings of the National Academy of Sciences.

The most disabling form of mental illness, schizophrenia affects one percent of the adult population, typically in young adulthood, with hallucinations, delusions, social withdrawal, flattened emotions and loss of social and personal care skills. Although its cause remains a mystery, evidence suggests that it is at least 80% heritable, stemming from complex interactions among several genes and non-genetic influences. Several chromosomal regions have been implicated, but none have been definitely confirmed and no genes have yet been linked to the disorder.

Given the syndrome's daunting complexity, Weinberger and colleagues have been studying many traits to identify those that patients share with their well siblings, hoping to turn up clues to susceptibility genes. Their brain imaging studies had revealed that both well siblings and patients falter on tasks of working memory and show abnormal activation of the prefrontal cortex, which is required for such "executive" functions. Studies have shown that the chemical messenger dopamine plays a pivotal role in tuning the activity of the prefrontal cortex during such tasks.

A gene called COMT (catecho-o-methytransferase) had long been
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Contact: Jules Asher
jasher@nih.gov
301-443-7855
NIH/National Institute of Mental Health
27-May-2001